Terpenes and the Entourage Effect

Cannabinoids set the stage

Cannabis terpenes are volatile compounds packed with medicinal possibilities, but they’re not alone. They share space with the chemical substances that bind with receptors throughout the brain and body, known as cannabinoids. There have been over 100+ cannabinoids identified in the cannabis plant, and research shows these compounds play a role in multiple processes in mammals including the regulation of metabolic activity, digestion, and immune cell function. The endocannabinoid system facilitates cannabinoids’ ability to bind to the CB1 and CB2 receptors located throughout the body and central nervous system, resulting in myriad therapeutic outcomes. 

Δ9-Tetrahydrocannabinol (THC) is the cannabis plant’s principal chemical component and the cannabinoid attributed to a variety of its pharmacological functions – most notably its psychoactive and analgesic properties. Research has shown THC to be a partial agonist, able to initiate a physiological response when combined with CB1 and CB2 receptors. When cannabis is smoked, THC and its metabolites enter the bloodstream quickly through the lungs and within 10 minutes achieve peak levels throughout the body. While THC bioavailability reportedly averages around 30%, effects on bioavailability vary by consumption method. Inhaled THC is the most bioavailable at 10-35%; ingested THC is less bioavailable at 4-12% because it is quickly absorbed by fat tissue. 

The second most prevalent cannabinoid in the cannabis plant is cannabidiol or CBD, which is known to provide anti-anxiety, anti-inflammatory, and analgesic properties. CBD is absorbed quickly in the brain and throughout the body when consumed, and the fastest effects on bioavailability come via inhalation at an average of 11-45%. By comparison, the bioavailability of ingested CBD is about 6%. Considered to be non-psychoactive, CBD is shown to have potentially mitigating effects on the potency of THC. High levels of CBD have demonstrated the ability to reduce the intoxication associated with THC, while low doses of CBD may enhance THC’s therapeutic effects. This sets the foundation for the entourage effect theory.

What is the entourage effect?

In 1998, Professors Raphael Mechoulam and Shimon Ben-Shabat hypothesized that when the chemical compounds from cannabis were combined, they produced synergistic effects greater than the total sum of effects from each contributing part. Called the “entourage effect”, this theory established the framework that the greatest therapeutic benefit comes not from one individual compound but from the interaction between different cannabinoids as well as the combination of cannabinoids and terpenes.

The relationship between THC and CBD has led to the development of a variety of consumer options that leverage the synergistic relationship between these and other compounds found in the cannabis plant. Full-spectrum products, for example, blend extracts of CBD with terpenes, essential oils, flavonoids, and other cannabinoids – including lower concentrations of THC – while broad-spectrum products are higher in CBD and other plant constituents but have little-to-no THC.

Here’s how some of the other compounds from the cannabis plant factor into the entourage effect:

Cannabichromene (CBC)

The non-psychoactive cannabinoid cannabichromene, or CBC, is one of the most abundant cannabinoids in the cannabis plant. A key contributor to the plant’s anti-inflammatory properties, CBC also reportedly demonstrates antimicrobial, analgesic, and antidepressant potential. Research has shown CBC not to interact with CB1 and CB2 receptors to the same degree as THC and CBD, yet its ability to inhibit anandamide uptake has a direct influence on the body’s endocannabinoid system. According to one study, CBC has been found to play a role in the entourage effect by enhancing the cytotoxic properties of THC in the treatment of Urothelial Cell Carcinoma. CBC was also found to increase the effectiveness of CBD extracts.

Cannabigerol (CBG)

Considered to be “the mother of all cannabinoids”, cannabichromene aka CBG also abundantly appears in the cannabis plant. Like THC, CBG is a partial agonist of CB1 and CB2 receptors. CBG also shares CBD’s non-psychoactive traits and shows the potential to provide relief against pain, insomnia, anxiety, and depression. Preliminary research into the synergistic effects between the two most abundant non-psychoactive cannabinoids indicates that CBG is not as effective against inflammation by itself. But when administered with CBD, CBG was shown to contribute to the entourage effect by enhancing CBD’s anti-inflammatory properties. 

Cannabinol (CBN)

Cannabinol or CBN is an oxidized metabolite of THC and another abundant cannabinoid in the cannabis plant. While research into CBN is limited, studies on both animals and humans have shown CBN to produce sedative, anti-inflammatory, antibiotic, and anticonvulsant activity. CBN has about ¼ the potency of THC so it’s not completely non-psychoactive, but some research indicates that CBN may increase the sedative properties of both THC and CBD.

Tetrahydrocannabivarin (THCV)

Δ9- Tetrahydrocannabivarin or THCV is more than a letter’s difference from THC – it’s also non-psychoactive. While there’s still much to learn about THCV, some rodent studies show the cannabinoid’s potential appetite suppressive and neuroprotective properties. And according to one study, THCV could possess the ability to inhibit THC’s psychoactive effects. 

At its core, the entourage effect reinforces the belief that we may benefit more from the whole plant than from the isolation of its individual chemical components. And the more we discover about this possibility, the greater the therapeutic potential for all of us.